1-163198509-A-G

Position:

• chr1-163198509-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003617.4(RGS5):​c.44+4283T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 152,080 control chromosomes in the GnomAD database, including 23,609 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (23609 hom., cov: 33)
• Consequence: RGS5 NM_003617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.582

Genes affected

RGS5 (HGNC:10001): (regulator of G protein signaling 5) This locus represents naturally occurring readthrough transcription between the neighboring LOC127814295 (uncharacterized LOC127814295) and RGS5 (regulator of G-protein signaling 5) genes on chromosome 1. Some variants of the readthrough transcript encode novel proteins with unique N-termini. [provided by RefSeq, Nov 2022]

RGS5-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS5	NM_003617.4	c.44+4283T>C		intron_variant		ENST00000313961.10	NP_003608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS5	ENST00000313961.10	c.44+4283T>C		intron_variant		1	NM_003617.4	ENSP00000319308.5

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83259 AN: 151962 Hom.: 23587 Cov.: 33

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.515

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.548 AC: 83326 AN: 152080 Hom.: 23609 Cov.: 33 AF XY: 0.542 AC XY: 40304 AN XY: 74340

Gnomad4 AFR AF: 0.693

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.542

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.520

Gnomad4 OTH AF: 0.515

Alfa AF: 0.536 Hom.: 4918

Bravo AF: 0.546

Asia WGS AF: 0.464 AC: 1616 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2999965; hg19: chr1-163168299;